Cannabidiol (CBD), which is a non-psychoactive pharmacologically relevant constituent of Cannabis, demonstrates several beneficial effects. It has been found to have antioxidative, anti-inflammatory, and neuroprotective effects. As the medicinal use of CBD is gaining popularity for treatment of various disorders, the recent flare-up of largely unproven and unregulated cannabis-based preparations on medical therapeutics may have its greatest impact in the field of neurology.
CBD demonstrates remarkable potential to become a supplemental therapy in various neurological conditions. It has shown promise in the treatment of neurological disorders such as anxiety, chronic pain, trigeminal neuralgia, epilepsy, and essential tremors as well as psychiatric disorders.
While recent FDA-approved prescription drugs have demonstrated safety, efficacy, and consistency enough for regulatory approval in spasticity in multiple sclerosis (MS) and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges still remain. In this article, we will be highlighting the research which has shed light on the application of CBD in the management and treatment of various neurological disorders.
Cannabis (marijuana) is a psychoactive drug used for recreational purposes and is known to have adverse health effects. However, in the past several years, pharmacologically relevant constituents of cannabis, apart from THC, have gained attention from research and legislation. The most prominent of those is cannabidiol (CBD), which is nonintoxicating but demonstrates several beneficial pharmacological effects. It has been found to have physiological effects such as antioxidative, anti-inflammatory, and neuroprotection.
It is the current opinion of many that neurology is facing a therapeutic dead end. The existing single target receptor pharmacotherapy has not proven generally useful in the face of complex neurological diseases. As the medicinal use of CBD is expanding worldwide, it is gaining popularity for treatment of various neurologic disorders such as anxiety, chronic pain, trigeminal neuralgia, epilepsy, and essential tremors as well as psychiatric disorders. In the current review, the authors have shed light on the application of CBD in the management and treatment of various neurological disorders.
Historical Perspective on Cannabidiol (CBD)
Cannabis is a genus of flowering plants that has had a long history of usefulness since 1000 BC. There is early evidence suggesting that the Chinese and Indian populations used it for religious and medicinal purposes. It was not until 1839 that Cannabis was introduced into western medicine by W.B. O’Shaughessy. During this time Cannabis was being used for its analgesic and sedative properties in arthritic and epileptic patients, respectively. The increasing positive outcomes on patients’ health and the scarcity of side effects highlighted the practical therapeutic application of Cannabis. This encouraged scientists to explore the mechanisms responsible for its molecular and cellular actions.
- However, multiple shortcomings halted its therapeutic potential and scientific progress. These obstacles included pharmacodynamics, lack of standardized production protocols, governmental regulations, and the discovery of more effective treatments such as opiates.
CBD is non-psychoactive and the second most prevalent bioactive compound in Cannabis sativa. Therefore, because of its non-psychoactive properties and its relatively low toxicity and addiction profile, it has been considered for the treatment of various pathologies including chronic pain, essential tremor (ET), Parkinson’s (PD), obsessive compulsive disorder, and epilepsy. Recent clinical trials assessing the role of CBD in the above-mentioned conditions are demonstrating the potential role of CBD as adjuvant therapy where existing treatments are not entirely satisfactory.
Mechanisms of Action (MOA), Cannabidiol (CBD)
CBD’s anti-inflammatory actions can be explained by its activity on various receptors that decrease the migration of:
- leukocytes (part of the immune system that help fight infections or disease),
- inhibit the COX1 and COX2 pathways (inflammatory response pathways), and
- decrease the production of pro-inflammatory cytokines (cells that regulate inflammatory responses).
The human nervous system is impregnated with cannabinoid receptors, cannabinoid type 1 (CB1), and cannabinoid type 2 (CB2).
- CB1 is concentrated in the central nervous system and is believed to be responsible for psychological effects on pleasure, memory, thought, concentration, sensory and time perceptions, and coordinated movement.
- CB2 receptors are expressed mostly in peripheral tissues and immune cells thereby playing a role in inflammation.
Although CBD has low affinity for the CB2 receptor, at low doses it functions as an inverse agonist and antagonist that can block migration of immune cells and decrease inflammation. However, it is the CB2 receptor-independent actions that have a significant role in modulating inflammation. Their action here involves the modulation of pathways in the inflammatory process. In addition to its anti-inflammatory properties, CBD has antioxidant properties that have been shown to be neuroprotective.
Due to the diversity of CBD pharmacological applications, multiple drug delivery modalities are being considered for treatment. CBD is extracted from hemp and its bioavailability differs significantly with the mode of administration. If taken orally, CBD bioavailability ranges between 13 and 19%, as opposed to 31% when inhaled.
Current Applications in Neurology
- An early study in 2007 by Nurmikko illustrated > 30% improvement in subjective peripheral neuropathy pain ratings in 26% of patients receiving analgesic therapy with Nabiximols (oromucosal CBD spray).
- In the realm of arthritis pain relief, an RCT in patients with rheumatoid arthritis reported statistically significant improvements in analgesia and sleep quality in patients receiving Nabiximols vs. the placebo-controlled group. Overall, these promising results thus far along with the favorable safety profile warrant further research into the use of Nabiximols for chronic non-cancer-related pain.
Parkinson’s Disease (PD)
- Of the few studies completed, most of the statistically significant benefits of CBD in PD patients have been related to subjective quality of life improvements and reductions in symptoms related to PD-related psychosis.
- A 2014 case report in 4 PD patients revealed reduction (and in some cases complete elimination) of agitation, kicking, nightmare, and/or aggressive behavior in PD patients with comorbid REM sleep behavior disorder who were treated with oral doses of CBD
- When it comes to the effectiveness of CBD in alleviating PD-related tremor, an early study in PD patients reported dose-related improvements in movement symptoms (ranging from 20 to 50%) in patients treated over a 6-week period with oral doses of CBD.
Trigeminal Neuralgia (TN)
- Numerous studies have highlighted a remarkable degree of effectiveness of a cannabis-related substance in alleviating TN pain in humans, which certainly merits further study. The variety of molecular mechanisms by which CBD can achieve analgesic effects illustrates its undeniable potential as an alternative solution to treat patients suffering from refractory (treatment resistant, or TR) TN.
There is currently only one FDA-approved CBD prescription drug being used to treat two rare genetic epilepsy syndromes. However, with ongoing clinical trials and tremendous research in the pharmaceutical industry, CBD has a remarkable potential to become a supplemental therapy in various healthcare domains including pain, neuro-cognitive diseases, and neuro-psychiatric syndromes.